title: Review article: the association between nodular regenerative hyperplasia, inflammatory bowel disease and thiopurine therapy.
abstract: BACKGROUND
  Nodular regenerative hyperplasia (NRH) is increasingly being recognised in patients with inflammatory bowel disease (IBD). However, the pathogenesis and incidence of NRH in IBD, and the putative roles played by azathioprine (AZA), mercaptopurine (MP), or tioguanine (TG) remain unclear.
  
  
  OBJECTIVE
  To summarise the data on the association between NRH and thiopurine therapy in patients with IBD.
  
  
  METHODS
  A literature search was performed in PubMed and MEDLINE databases using the keywords 'nodular regenerative hyperplasia AND (inflammatory bowel disease OR Crohn's disease OR ulcerative colitis) AND (azathioprine OR mercaptopurine OR tioguanine OR thioguanine).' No time limit was placed on studies included.
  
  
  RESULTS
  Inflammatory bowel disease patients treated with AZA have a cumulative incidence of NRH of approximately 0.6% and 1.28% at 5 and 10 years, respectively, whereas those treated with high-dose TG (>40 mg/day) have a frequency of NRH of up to 62%, which is higher in patients with elevated liver enzymes and/or thrombocytopaenia than those without these abnormalities (frequency 76% vs. 33%). Conversely, low-dose TG therapy (<20 mg/day) is relatively safe, with no cases of NRH observed. NRH has also been found in 6% of operated thiopurine-naïve IBD patients. Male gender, older age, and stricturing disease/small bowel resection have been consistently identified as high-risk factors for NRH.
  
  
  CONCLUSIONS
  The pathogenesis of nodular regenerative hyperplasia in patients with IBD is complex and multifactorial involving disease-specific, genetic and iatrogenic risk factors. Clinicians should maintain a high index of suspicion for diagnosing nodular regenerative hyperplasia, especially in IBD patients with high-risk factors on thiopurine therapy, regardless of the presence of laboratory abnormalities.
authors.affiliation: Department of Gastroenterology and Hepatology, The Royal Liverpool and Broadgreen University Hospitals NHS Trust, Liverpool, UK.
authors.forename: C O
authors.initials: CO
authors.lastname: Musumba
mesh_terms: D001379:Azathioprine / Q000009:adverse effects / Q000627:therapeutic use; D003093:Colitis, Ulcerative / Q000188:drug therapy*; D003424:Crohn Disease / Q000188:drug therapy*; D005260:Female; D020518:Focal Nodular Hyperplasia / Q000453:epidemiology / Q000209:etiology*; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000627:therapeutic use; D015994:Incidence; D008297:Male; D015122:Mercaptopurine / Q000009:adverse effects / Q000627:therapeutic use; D012307:Risk Factors; D013866:Thioguanine / Q000009:adverse effects / Q000627:therapeutic use; D013997:Time Factors
chemical_list: D007166:Immunosuppressive Agents; D015122:Mercaptopurine; D013866:Thioguanine; D001379:Azathioprine